Organic Chemistry

1
Organic Chemistry

• William H. Brown
• Christopher S. Foote
• Brent L. Iverson

2
Mass Spectrometry
Chapter 14

• Chapter 12

3
Mass Spectrometry (MS)

• An analytical technique for measuring the
  mass-to-charge ratio (m/z) of ions in the gas
  phase
• mass spectrometry is our most valuable analytical
  tool for determining accurate molecular masses
• also can give information about structure
• proteins can now be sequenced by MS

4
Mass Spectrometry (MS)
5
A Mass Spectrometer

• A mass spectrometer is designed to do three
  things
• convert neutral atoms or molecules into a beam of
  positive (or negative) ions
• separate the ions on the basis of their
  mass-to-charge (m/z) ratio
• measure the relative abundance of each ion

6
A Mass Spectrometer

• Electron Ionization MS
• in the ionization chamber, the sample is
  bombarded with a beam of high-energy electrons
• collisions between these electrons and the sample
  result in loss of electrons from sample molecules
  and formation of positive ions

7
Molecular Ion

• Molecular ion (M) a radical cation formed by
  removal of a single electron from a parent
  molecule in a mass spectrometer
• For our purposes, it does not matter which
  electron is lost radical cation character is
  delocalized throughout the molecule therefore,
  we write the molecular formula of the parent
  molecule in brackets with
• a plus sign to show that it is a cation
• a dot to show that it has an odd number of
  electrons

8
Molecular Ion

• at times, however, we find it useful to depict
  the radical cation at a certain position in order
  to better understand its reactions

9
Mass Spectrum

• Mass spectrum a plot of the relative abundance
  of ions versus their mass-to-charge ratio
• Base peak the most abundant peak
• assigned an arbitrary intensity of 100
• The relative abundance of all other ions is
  reported as a of abundance of the base peak

10
MS of dopamine

• a partial MS of dopamine showing all peaks with
  intensity equal to or greater than 0.5 of base
  peak

11
MS of Dopamine

• the number of peaks in the MS spectrum of
  dopamine is given here as a function of detector
  sensitivity

12
Other MS techniques

• What we have described is called electron
  ionization mass spectrometry (EI-MS)
• Other MS techniques include
• fast atom bombardment (FAB)
• matrix-assisted laser desorption ionization
  (MALDI)
• chemical ionization (CI)
• electrospray ionization (ESI)

13
Resolution

• Resolution a measure of how well a mass
  spectrometer separates ions of different mass
• low resolution refers to instruments capable of
  separating only ions that differ in nominal mass
  that is ions that differ by at least 1 or more
  atomic mass units
• high resolution refers to instruments capable of
  separating ions that differ in mass by as little
  as 0.0001 atomic mass unit

14
Resolution

• C3H6O and C3H8O have nominal masses of 58 and 60,
  and can be distinguished by low-resolution MS
• C3H8O and C2H4O2 have nominal masses of 60
• distinguish between them by high-resolution MS

15
Isotopes

• virtually all elements common to organic
  compounds are mixtures of isotopes

16
Isotopes

• carbon, for example, in nature is 98.90 12C and
  1.10 113C
• there are 1.11 atoms of carbon-13 in nature for
  every 100 atoms of carbon-12

17
M2 and M1 Peaks

• The most common elements giving rise to
  significant M 2 peaks are chlorine and bromine
• chlorine in nature is 75.77 35Cl and 24.23 37Cl
  
• a ratio of M to M 2 of approximately 31
  indicates the presence of a single chlorine in a
  compound

18
M2 and M1 Peaks

• bromine in nature is 50.7 79Br and 49.3 81Br
• a ratio of M to M 2 of approximately 11
  indicates the presence of a single bromine in a
  compound

19
M2 and M1 Peaks

• Sulfur is the only other element common to
  organic compounds that gives a significant M 2
  peak
• 32S 95.02 and 34S 4.21
• Because M 1 peaks are relatively low in
  intensity compared to the molecular ion and often
  difficult to measure with any precision, they are
  generally not useful for accurate determinations
  of molecular weight

20
Fragmentation of M

• To attain high efficiency of molecular ion
  formation and give reproducible mass spectra, it
  is common to use electrons with energies of
  approximately 70 eV 6750 kJ (1600 kcal)/mol
• this energy is sufficient not only to dislodge
  one or more electrons from a molecule, but also
  to cause extensive fragmentation
• these fragments may be unstable as well and, in
  turn, break apart to even smaller fragments

21
Fragmentation of M

• Fragmentation of a molecular ion, M, produces a
  radical and a cation
• only the cation is detected by MS

22
Fragmentation of M

• A great deal of the chemistry of ion
  fragmentation can be understood in terms of the
  formation and relative stabilities of
  carbocations in solution
• where fragmentation occurs to form new cations,
  the mode that gives the most stable cation is
  favored
• the probability of fragmentation to form new
  carbocations increases in the order

23
Interpreting MS

• The only elements to give significant M 2 peaks
  are Cl and Br
• if no large M 2 peak is present, these elements
  are absent
• Is the mass of the molecular ion odd or even?
• Nitrogen Rule if a compound has
• zero or an even number of nitrogen atoms, its
  molecular ion will have an even m/z value
• an odd number of nitrogen atoms, its molecular
  ion will have an odd m/z value

24
Alkanes

• Fragmentation tends to occur in the middle of
  unbranched chains rather than at the ends
• The difference in energy among allylic, benzylic,
  3, 2, 1, and methyl cations is much greater
  than the difference among comparable radicals
• where alternative modes of fragmentation are
  possible, the more stable carbocation tends to
  form in preference to the more stable radical

25
Alkanes

• MS of octane (Fig 14.5)

26
Alkanes

• MS of 2,2,4-trimethylpentane (Fig 14.6)

27
Alkanes

• MS of methylcyclopentane (Fig 14.7)

28
Alkenes

• Alkenes characteristically
• show a strong molecular ion peak
• cleave readily to form resonance-stabilized
  allylic cations

29
Cyclohexenes

• cyclohexenes give a 1,3-diene and an alkene, a
  process that is the reverse of a Diels-Alder
  reaction (Section 24.3)

30
Alkynes

• Alkynes typically
• show a strong molecular ion peak
• cleave readily to form the resonance-stabilized
  propargyl cation or a substituted propargyl cation

31
Alcohols

• One of the most common fragmentation patterns of
  alcohols is loss of H2O to give a peak which
  corresponds to M-18
• Another common pattern is loss of an alkyl group
  from the carbon bearing the OH to give a
  resonance-stabilized oxonium ion and an alkyl
  radical

32
Alcohols

• MS of 1-butanol (Fig 14.8)

33
Aldehydes and Ketones

• Characteristic fragmentation patterns are
• cleavage of a bond to the carbonyl group
  (?-cleavage)
• McLafferty rearrangement

34
Aldehydes and Ketones

• MS of 2-octanone (Fig 14.9)

35
Carboxylic Acids

• Characteristic fragmentation patterns are
• ?-cleavage to give the ion CO2H of m/z 45
• McLafferty rearrangement

36
Carboxylic Acids

• MS of butanoic acid (Fig 14.12)

37
Esters

• ?-cleavage and McLafferty rearrangement

38
Esters

• MS of methyl butanoate (Fig 14.13)

39
Aromatic Hydrocarbons

• most show an intense molecular ion peak
• most alkylbenzenes show a fragment ion of m/z 91

H
H

H

H

H
H
H
40
Amines

• The most characteristic fragmentation pattern of
  1, 2, and 3 aliphatic amines is ?-cleavage

41
Mass Spectrometry
End Chapter 14